Distinct Serum and Vitreous Inflammation-Related Factor Profiles in Patients with Proliferative Vitreoretinopathy.

INTRODUCTION: Proliferative vitreoretinopathy (PVR), which is regulated by growth factors and cytokines, is the leading cause of failure in vitreoretinal surgery. In this study, we aimed to investigate the role of the human serum and vitreous inflammation-related factors in the development of proliferative vitreoretinopathy (PVR). METHODS: Blood and vitreous samples were obtained from patients undergoing pars plana vitrectomy. Inflammation-related factors were detected using an immunology multiplex assay on a Luminex® xMAP® platform. Patients with PVR and rhegmatogenous retinal detachment (RRD) were compared with macular hole (MH) or epiretinal membrane (ERM) patients without any other ocular or systemic disease. RESULTS: Thirty-six serum samples and 34 vitreous samples were obtained. Thirty-one different growth factors and cytokines were detected in serum samples. However, none of the circulating growth factors and cytokines were found to be different from the controls. Ten different growth factors and cytokines were measured in the vitreous samples. The concentration levels of PDGF-AA, TGF-α, VEGF, IL-6, IL-8, and TNFß were found to have significantly increased in the vitreous of PVR patients. CONCLUSION: Our study found that none of the circulating inflammation-related factors were changed in PVR or RRD patients, indicating the absence of a system inflammatory biomarkers to predict the development of proliferative vitreoretinopathy. As a supplement to previous research, the concentrations of PDGF-AA, TGF-α, VEGF, IL-6, IL-8, and TNFß were significantly upregulated in the vitreous of PVR patients. These factors should be considered for preventing PVR.

Th17 cell frequency and IL-17A concentrations in peripheral blood mononuclear cells and vitreous fluid from patients with diabetic retinopathy.

Objective To quantify T helper (Th)17 cells and determine interleukin (IL)-17A levels in peripheral blood mononuclear cell (PBMC) culture and vitreous fluid from patients with type 2 diabetes mellitus (T2DM) with diabetic retinopathy (DR). Methods Th17 cell frequency and IL-17A concentrations in PBMCs from 60 patients with T2DM with DR, 30 without DR and 30 sex- and age-matched healthy individuals were measured by flow cytometry and enzyme-linked immunosorbent assay (ELISA), respectively. IL-17A levels in vitreous fluid from 31 eyes with proliferative DR and diabetic macular oedema (DR group) and 32 eyes with an epiretinal membrane and macular hole (control group) that underwent vitrectomy were also examined by ELISA. Results Compared with the control group, the proportion of Th17 cells and IL-17A concentrations in PBMCs were significantly increased in patients without DR but decreased in those with DR. IL-17A concentrations and Th17 cell frequency in PBMCs tended to decrease with DR severity and were negatively correlated with body mass index, T2DM duration and glycated haemoglobin. Additionally, vitreous fluid IL-17A levels were significantly elevated in patients with DR compared with those of the control group. Conclusions We conclude that disturbances in Th17 cells and IL-17A levels are possibly associated with DR.

Epiretinal membrane in a 12-year-old immunocompetent girl with cytomegalovirus infection.

PURPOSE: To report the case of a 12-year-old immunocompetent girl presenting bilateral epiretinal membrane formation in conjunction with systemic human cytomegalovirus (HCMV) infection. METHODS: The patient had a sudden onset of blurred vision and floaters in both eyes. Her medical history was unremarkable, except for allergic asthma that she had had for several years and that she was treating with inhaler corticosteroids prescribed by her pediatrician. The patient underwent a complete ophthalmic examination and serologic blood test. RESULTS: The ocular examination revealed an epiretinal membrane confirmed by optical coherence tomography, which showed a band of high optical reflectivity compatible with a proliferation of abnormal tissue on the surface of the retina. The patient had serologic evidence of exposure to HCMV, which was verified by a strongly positive HCMV IgM antibody test result (320 IU), with detectable IgG antibodies against HCMV, which significantly rose further in consecutive blood samples, due to IgG antibody seroconversion. CONCLUSIONS: Our patient had allergic asthma that she was treating with inhaled corticosteroids. The immunosuppressive properties of corticosteroids could induce endogenous reactivation of latent HCMV.

Proliferative diabetic retinopathy with lymphocyte-rich epiretinal membrane associated with poor visual prognosis.

PURPOSE: The aim of this study was to analyze lymphocyte infiltration using immunohistochemistry in proliferative diabetic retinopathy (PDR) membranes. METHODS: Sixteen patients, 13 with PDR and 3 without diabetes, underwent pars plana vitrectomy, and the epiretinal membrane was peeled. Formalin-fixed, paraffin-embedded epiretinal membrane tissues were processed for immunohistochemistry with anti-leukocyte common antigen (LCA), CD3, and CD20 antibodies. Lymphocyte density was determined by direct counting at a high magnification under a light microscope, which was compared with the patients' visual prognoses. RESULTS: The lymphocyte density ranged from 1 to 52 (mean, 9.5) in high-power fields. Of 13 membranes, 5 showed a lymphocyte density of >5 cells, whereas the other 8 membranes showed a cell number of <2. The former type is defined as a lymphocyte-rich epiretinal membrane (LERM). Infiltrated lymphocytes were immunohistochemically positive for CD3, a T-cell marker, but not for CD20, a B-cell marker. All patients with LERM had poor visual prognosis after vitrectomy. In contrast, the visual prognosis in 7 patients with non-LERM improved or remained unchanged. A significant association was observed between high-level lymphocyte infiltration in the epiretinal membrane and poor visual prognosis (P < 0.001). LCA(+) mononuclear cells were not observed in epiretinal membranes in the absence of diabetes. CONCLUSIONS: These results suggest that the high-level infiltration of T lymphocytes into the PDR membrane is well correlated with poor visual prognosis. Histopathologic observation of the epiretinal membrane in patients with PDR may provide significant prognostic information.

Immunopathology of intraocular silicone oil: retina and epiretinal membranes.

AIMS: To determine the inflammatory response in retina and epiretinal membranes after intraocular silicone oil tamponade. METHODS: 14 proliferative vitreoretinopathy (PVR) epiretinal membranes, 33 retro-oil epiretinal membranes, 19 retinectomies, 14 retro-oil retinectomies and 37 idiopathic epiretinal membranes (controls) underwent immunohistochemical analysis using the avidin-biotin complex technique and a panel of monoclonal and polyclonal antibodies. The number of positive cells counted in five 0.5 mm diameter fields of immunohistochemical sections was graded on a score of 1-4. RESULTS: Macrophage cell counts were significantly greater in membranes with a history of exposure to silicone oil (p<0.001). An inflammatory response could be observed within 1 month of silicone oil exchange, and the intensity seemed to be unrelated to the duration of exposure. Macrophages were confined to epiretinal membranes on the surface of retinectomy specimens in 10 of 14 cases and intraretinal macrophages were observed only in specimens with gliotic retina. T and B lymphocytes were rarely seen in the specimens examined. Marked glial cell up regulation was observed in 11 of 16 retinectomy specimens and in 8 of 11 retro-oil retinectomies. Glial cell content was variable in the membranes, but there was a trend of increased presence after exposure to silicone oil. CONCLUSION: This study has shown that the use of silicone oil is accompanied by an inflammatory reaction, primarily mediated by bloodborne macrophages. This response can be observed within 1 month of silicone oil injection and continues after silicone oil removal. Retinal surgeons should be aware of the potential secondary effects of intraocular silicone oil when they are considering its use (and removal) in vitreoretinal surgery.

The immunological studies on proliferative intraocular disorders: investigation of activated lymphocytes, macrophages and HLA-DR.

PURPOSE: To investigate whether activated B lymphocytes (CD23), activated T lymphocytes (CD25), macrophages (CD68) and human leucocyte antigen class II antigen (HLA-DR) were existed in epiretinal membranes (ERMs) and subretinal membranes (SRMs) of proliferative intraocular disorders (PID). METHODS: Twenty specimens of ERMs from rhegmatogenous retinal detachment with proliferative vitreoretinopathy (PVR), traumatic PVR and secondary traction retinal detachment, and two specimens of SRMs from rhegmatogenous retinal detachment with PVR and traumatic PRV were studied using immunohistochemical staining. RESULTS: CD68 and HLA-DR were found in all specimens, CD23 and CD25 in 4 cases of ERMs and in 1 case of SRMs, respectively. CONCLUSIONS: 1. The ERMs and SRMs of different etiology shared a common basis of inflammation and immunopathology. 2. There would be secondary cellular and humoral immunity in the ERMs and the SRMs of PID.